Rabih Shakib Talhouk

American University of Beirut | AUB · Department of Biology

Inflammation is associated with the development of several cancers, including breast cancer. However, the molecular mechanisms driving breast cancer initiation or enhancement by inflammation are yet to be deciphered. Hence, we opted to investigate the role of inflammation in initiating and enhancing tumor-like phenotypes in nontumorigenic, pretumor...

Breast cancer (BC) is the most predominant type of cancer among women. The aim of this study is to find new biomarkers that can help in early detection of BC, especially for those who are too young to be screened using mammography as per guidelines. Using microRNA microarray, we previously showed dysregulation of 74 microRNAs in tumors from early B...

Background Breast cancer, the most commonly diagnosed malignancy in women, accounts for the highest cancer-related deaths worldwide. Triple negative breast cancer (TNBC), lacking the expression of estrogen, progesterone and HER2 receptors, has an aggressive clinical phenotype and is susceptible to chemotherapy but not to hormonal or targeted immuno...

With the increase in knowledge on the importance of the tumor microenvironment, cell culture models of cancers can be adapted to better recapitulate physiologically relevant situations. Three main microenvironmental factors influence tumor phenotype: the biochemical components that stimulate cells, the fibrous molecules that influence the stiffness...

Cell–cell communication is essential for tissue homeostasis, but its contribution to disease prevention remains to be understood. We demonstrate the involvement of connexin 43 (Cx43, also known as GJA1) and related gap junction in epithelial homeostasis, illustrated by polarity-mediated cell cycle entry and mitotic spindle orientation (MSO). Cx43 l...

(1) Background: The expression of connexin 43 (Cx43) is disrupted in breast cancer, and re-expression of this protein in human breast cancer cell lines leads to decreased proliferation and invasiveness, suggesting a tumor suppressive role. This study aims to investigate the role of Cx43 in proliferation and invasion starting from non-neoplastic bre...

Connexins (Cxs), the building blocks of gap junctions (GJs), exhibit spatiotemporal patterns of expression and regulate the development and differentiation of the mammary gland, acting via channel-dependent and channel-independent mechanisms. Impaired Cx expression and localization are reported in breast cancer, suggesting a tumor suppressive role...

Studies demonstrated loss of connexin 43 (Cx43) expression in breast cancer cells in-vitro and in-vivo. Our previous studies have shown that silencing Cx43 in HMT-3522 S1 cells, non-neoplastic human mammary epithelial cells (S1 cells), altered apical polarity and mitotic spindle orientation under 3-dimensional (3-D) culture conditions. The purpose...

Matricaria chamomilla (L.), and Matricaria aurea (Loefl.) Sch. Bip., are two threatened wild species commonly used for medicinal purposes in Lebanon. An eco-geographic study was conducted, by assessing the distribution pattern of the two species in Lebanon and their related genetic diversity, to guide conservation efforts. The constructed distribut...

Breast cancer (BC) has a higher incidence in young Lebanese woman as compared to the West. We assessed the microRNA (miRNA) microarray profile of tissues derived from Lebanese patients with early BC and performed mRNA-miRNA integration analysis. 173 miRNAs were significantly dysregulated in 45 BC versus 17 normal adjacent breast tissues, including...

A sesquiterpene lactone 1-β,10-Epoxy-6-hydroxy-1,10H-inunolide (K100) was isolated through “bioassay-guided fractionation” from Cota palaestina subsp. syriaca, an Eastern Mediterranean endemic plant. K100 inhibited endotoxin- (ET-) induced proinflammatory markers: IL-6, MMP-9, and NO in normal mouse mammary SCp2 Cells. Molecular docking in silico s...

Relative to western populations, the percentage of women diagnosed with breast cancer at a young age in Lebanon is high. While the younger age of the Lebanese population compared to the West certainly contributes to this difference, potential genetic, reproductive and/or biological factors likely play an important role. The objective of this study...

Understanding the biology of the mammary gland is essential for deciphering the molecular mechanisms behind breast cancer, a leading cause of death in women worldwide. There has been a dramatic shift from a genetic to a mixed genetic/epigenetic perception of breast cancer. Indeed, the expression of genes involved in mammary gland development is not...

Dietary supplements are used as preventive means to maintain a healthy state. Among them, polyunsaturated fatty acids (PUFAs), specifically members of the omega (n)-3 series and conjugated linoleic acid (CLA), have become the focus of extensive nutritional research in the last decade [1-6] due to their reported anti-inflammatory properties. Indeed,...

Connexins (Cx), gap junction (GJ) proteins, are regarded as tumor suppressors, and Cx43 expression is often down regulated in breast tumors. We assessed the effect of Cx43 over-expression in 2D and 3D cultures of two breast adenocarcinoma cell lines: MCF-7 and MDA-MB-231. While Cx43 over-expression decreased proliferation of 2D and 3D cultures of M...

Remarkable strides have been made in understanding the role of the extracellular matrix in mammary gland biology. But future efforts should employ a more physiologically relevant model system (i.e., a non-culture-based system).

Infl ammation is a physiologic response of the organism’s immune system to tissue damage caused by harmful stimuli like mechanical trauma, tissue necrosis, and infection. It is characterized clinically by cardinal symptoms described more than 2000 years ago: calor (heat), rubor (redness), dolor (pain), and loss of function. Although it is generally...

Crosstalk between gap junction intracellular communication (GJIC), STAT5 and OCT-1 in gap junction (GJ)-dependent β-casein expression was investigated. CID-9 mammary cells plated with prolactin on non-adherent substratum (poly-HEMA) expressed β-casein independent of STAT5 only in the presence of the GJIC inducer, cAMP. Nuclear STAT5 levels were not...

Gap junctions (GJ) can no longer be thought of as simple channel forming structures that mediate intercellular communication. Hemi-channel and channel-independent functions of connexins (Cxs) have been described and numerous Cx interacting partners have been uncovered ranging from enzymes to structural and scaffolding molecules to transcription fac...

The mammary gland presents a valuable model for developmental studies, spanning the embryonic stage through menarche to menopause. The dynamic remodeling of this gland is orchestrated by cellular heterogeneity, integrating mammogenic, systemic and local cues. Gap junctional intercellular communication provides pivotal cross talk of mammary epitheli...

IL-6 is a pro-inflammatory cytokine that signals via binding to a soluble or membrane bound receptor, while nitric oxide (NO), an oxidative stress molecule, diffuses through the cell membrane without a receptor. Both mediators signal through different mechanisms, yet they are dependent on NFκB. We proposed that both mediators are co-induced and co-...

Acute hypoxia at postnatal day (P) 10 is an accepted model of human neonatal hypoxia which results, among other consequences, in increased hippocampal excitability. Hypoxic-ischemic injury, which mimics stroke, has been shown to result in changes in connexins (Cxs), however, changes in Cxs have not been studied in the P10 hypoxia model. The aim of...

Medicinal plants represent alternative means for the treatment of several chronic diseases, including inflammation. The genus Ranunculus, a representative of the Ranunculaceae family, has been reported to possess anti-inflammatory, analgesic, antiviral, antibacterial, antiparasitic and antifungal activities, possibly due to the presence of anemonin...

Water extracts of Onopordum cynarocephalum (Oc) and Achillea damascena (Ad), traditionally used in Lebanon to treat various medical conditions including inflammatory diseases, were evaluated for anti-inflammatory activities employing an in vitro model of endotoxin (ET)-induced inflammation in mammary epithelial SCp2 cells and an in vivo model of ET...

Background Anti-inflammatory activities of medicinal plants have largely been attributed to their content of sesquiterpene lactones (SLs). SLs are predominantly found in the sunflower family Asteraceae and have been isolated from many plants of this family, particularly Centaurea. The anti-inflammatory activities of extract of Centaurea ainetensis,...

Inflammatory processes are characterized by the stimulation of humoral and cellular mediator systems resulting in increased levels of mediators of inflammation such as interleukins (ILs) and prostaglandins (PGs), which play central roles in regulating the inflammatory response and inflammation-mediated damage. The aim of the study was to develop na...

Connexins constitute a large family of trans-membrane proteins that allow intercellular communication and the transfer of ions and small signaling molecules between cells. Recent studies have revealed complex translational and post-translational mechanisms that regulate connexin synthesis, maturation, membrane transport and degradation that in turn...

Gap junctions (GJ) are required for mammary epithelial differentiation. Using epithelial (SCp2) and myoepithelial-like (SCg6) mouse-derived mammary cells, the role of heterocellular interaction in assembly of GJ complexes and functional differentiation (beta-casein expression) was evaluated. Heterocellular interaction is critical for beta-casein ex...

Of a selected 29 plants endemic to Lebanon and claimed to have anti-inflammatory effects, according to Lebanese folk literature, Centaurea ainetensis was chosen to further characterize its claimed anti-inflammatory activity using in-vitro and in-vivo assays. Water extract from C. ainetensis, at non-cytotoxic concentrations, inhibited in a dose depe...

Brain hypoxia-ischemia is a relatively common and serious problem in neonates and in adults. Its consequences include long-term histological and behavioral changes and reduction in seizure threshold. Gap junction intercellular communication is pivotal in the spread of hypoxia-ischemia related injury and in mediating its long-term effects. This revi...

The medical ethnobotanical knowledge propagated over generations in the coastal regions of the Eastern Mediterranean, including Lebanon, is one that has built on several ancient cultures and civilizations of these regions. Recent interest in medical ethnobotany and the use of medicinal herbs in treating or preventing ailments has rejuvenated intere...

An in vitro co-culture model of SCp2 mammary epithelial cells and Escherichia coli strains was established in bacterial non-CO(2) incubators. Co-culturing SCp2 cells with either the rod-shaped W3110 or spherical-shaped GC7378Tn10 strains of Escherichia coli led to an increase in interleukin-6 (IL-6) levels by SCp2 cells after 9 h. At a ratio of 1:1...

The mammary gland reaches a fully differentiated phenotype at lactation, a stage characterized by the abundant expression of beta-casein. We have investigated the expression and regulation of gap junction proteins (connexins, Cx) during the various developmental stages of mouse mammary gland. Immunohistochemical analysis, with specific antibodies,...

In this study it was determined that a Calendula officinalis water extract can reduce the immune response to three different viruses in broiler chickens, associated with improvement in body weights. The experiment was conducted on broiler chickens divided into two groups of 105 birds each. The first group received a Calendula officinalis water extr...

During inflammatory processes, the hypothalamic-pituitary axis is activated which can subsequently result in analgesia. For example, hypothalamic corticotrophin-releasing hormone (CRH) that is released during such activation has been attributed with analgesic actions. It is believed that the somatotrophic axis is also activated during inflammation....

The objective of this study is to test in vitro the antimicrobial efficacy of 39 water and 39 methanol extracts derived from different parts of 27 indigenous wild plant species that have been commonly used in Lebanese folk medicine. The antimicrobial efficacy was determined using the single disk diffusion method, with 10 and 20 microl load extract...

The effect of endotoxin on mammary CID-9 cells, which differentiate in culture and express beta-casein, was investigated. Cells in culture supplemented with lactogenic hormones and dripped with EMS-Matrix (EMS-drip), were treated daily with endotoxin (0.5-500 microg/ml). Endotoxin at concentrations of less or equal to 10 microg/ml did not affect ce...

Extravasation of tumor cells through the endothelial barrier is a critical step in cancer metastasis. Human T-cell lymphotropic virus type I (HTLV-I)-associated adult T-cell leukemia/lymphoma (ATL) is an aggressive disease characterized by visceral invasion. We show that ATL and HTLV-I-associated myelopathy patients exhibit high plasma levels of fu...

Gap junctions play a critical role in the development and differentiation of many tissues. Formed by the joining of two connexons on opposing membranes of two cells, gap junctions permit passage of ions and small molecules. Six connexins (Cx) belonging to a family of closely related tetraspan transmembrane proteins form a connexon. Connexin express...

The effect of dieldrin (Dln) on the development of the mammary gland and on functional parameters of CID-9 mammary cells in culture was investigated. One-month-old Sprague-Dawley female rats were bred and received intraperitoneal injection with 2.5 or 15 microM Dln during the last trimester of their gestation. Mammary glands of 15-microM Dln-treate...

Ionizing radiation (IR) is a known human breast carcinogen. Although the mutagenic capacity of IR is widely acknowledged as the basis for its action as a carcinogen, we and others have shown that IR can also induce growth factors and extracellular matrix remodeling. As a consequence, we have proposed that an additional factor contributing to IR car...

The relationship between gap junctional intercellular communication (GJIC) and mammary cell (CID-9) differentiation in vitro was explored. CID-9 cells differentiate and express beta-casein in an extracellular matrix (ECM)- and hormone-dependent manner. In response to interaction with the ECM, cells in culture modulated the expression of their gap j...

Developmental regulation of growth promoting activities in mammary secretions of pregnant Awassi ewes was defined, and growth factors contained in these secretions were partially purified and characterised. Mammary secretions from pregnant ewes enhanced fibroblast cell (AKR-2B) and mammary cell (CID-9 cell strain) proliferation to levels comparable...

American University of Beirut Medical Center, Lebanon. To assess the performance of a polymerase chain reaction (PCR) using primers that flank 542 bp within IS6110 in Mycobacterium tuberculosis (TB) vs. microscopy and BACTEC culture, in the diagnosis of tuberculosis. A total of 82 clinical respiratory pulmonary specimens and 73 samples from BACTEC...

The role of ECM-degrading proteinases in normal developmental processes and in pathological conditions is extensively studied. However, few reports describe the role ECM-degrading proteinases play in modulating hyperalgesia. The goal of this study is to describe the regulation of gelatinases during endotoxin mediated local inflammation, induced by...

This study investigates the first emergence of Salmonella Enteritidis outbreaks among chickens in the Lebanon and identifies the epidemiological markers of selected recovered Enteritidis strains. In addition, the authors evaluate a competitive exclusion approach to control infection in broiler chickens by Enteritidis organisms which possess the pre...

Milk samples were collected from 32 nursing mothers living in the Beirut area, Lebanon. Dietary intakes of participating mothers were obtained from data of their diet histories, 24 h dietary recalls and food frequency questionnaires. Milk samples were screened for the presence of organochlorine pesticide residues and DDE levels were estimated using...

Conventional and molecular techniques are being used in the detection of methicillin resistance in Staphylococcus aureus but they do not always show concordant results. In this study, a mecA PCR-based amplification was compared with the 1 microg oxacillin disk diffusion test and the Epsilometer test (E-test) for detection of MICs. Among 31 isolates...

Recovery of Campylobacter was attempted from 281 consecutive non selected out-patients diarrheic stools, 150 individual ceca collected from meat chicken breeder farms and 31 slaughtered marketed chicken obtained from shops in Lebanon. Campylobacter isolates were recovered from 2 (0.7%) human stool specimens, 34 (22.7%) chicken ceca and 3 (9.7%) raw...

The role of extracellular matrix in morphology, growth and lactoferrin synthesis and secretion in bovine mammary cells from a developing gland is poorly defined. In this study, bovine mammary cells from a hormone-primed developing gland were isolated and cultured on plastic, collagen, embedded within collagen, or on EHS-matrix, with the hormones pr...

Milk is now known to contain an array of bioactivities which extends the range of influence of mother over young beyond nutrition alone. Bioactivities in milk include modulators of digestive and gastrointestinal (GI) functions, hemodynamics (GI blood flow, hypertension), along with hormones and growth factors (mammary or infant development) probiot...

Three chicken broiler breeder flocks, 7 months of age, were confirmed to have Mycoplasma gallisepticum (MG) infection, based on culture of tracheal swabs. A total of fifty-five 7-day-old embryos from the three MG-positive flocks had an average 27.4% prevalence of MG-infection in their vitelline membrane. Sixty randomly selected MG isolates (30 from...

Milk is now recognized as containing an array of bioactivities that dramatically extend the range of influence of mother over young beyond simple nutrition. The bioactivities in milk include modulators of digestive and gastrointestinal (GI) functions, hemodynamic modulators with potential effects on the GI tract, hormones and growth factors likely...

We screened 110 DNA samples from carriers of beta-thalassaemia, using the ARMS-PCR technique with primers for common Mediterranean mutations. Unidentified samples were subjected to a heteroduplex analysis with Universal Heteroduplex Generators covering the beta-globin gene, followed by DNA sequencing. In total, 16 different mutations were detected,...

Bovine mammary gland secretions from several developmental stages were shown to stimulate [3H]thymidine incorporation into AKR-2B mouse embryo fibroblast cells. In virgin heifers, mammary secretions at 1% concentration stimulated thymidine incorporation into AKR-2B cells more than threefold compared with 10% (v/v) fetal calf serum. The growth-promo...